From the Journals

Antipsychotics linked to increased body fat, insulin resistance in children

View on the News

Stronger evidence of adverse metabolic effects

The findings of this study by Nicol and colleagues corroborate previous reports that used conventional anthropometry to document the metabolic adverse effects of second-generation antipsychotic medications in children and adolescents, according to authors of an accompanying editorial.

The current study used “gold standard” methods of measurement to demonstrate that 12 weeks of treatment with low-dose olanzapine, risperidone, or aripiprazole led to rapid-onset changes in adiposity and insulin sensitivity, with larger increases in those who received olanzapine.

“As such, the study even more emphatically underlines the risks to which these vulnerable populations are exposed,” Marc De Hert, MD, PhD, and Johan Detraux wrote.

It is now is clear that the potential psychiatric benefits of off-label antipsychotics need to be weighed against the potential for childhood-onset obesity and insulin resistance, they added. However, longer-term studies that use hard end points, such as new-onset diabetes or cardiovascular disease are needed.

Marc De Hert, MD, PhD, and Johan Detraux, are with Katholieke Universiteit Leuven, Kortenberg, Belgium. These comments are from an accompanying editorial (JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1080 ). Dr. De Hert reported no disclosures. Mr. Detraux reported partial support by the Janssen Academy for work on the the Belgian Discussion Board on Antipsychotic Treatment.



Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Next Article: